WO2017037296A1 - Produits d'addition stables d'acide 2-iodobenzoïque - Google Patents

Produits d'addition stables d'acide 2-iodobenzoïque Download PDF

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Publication number
WO2017037296A1
WO2017037296A1 PCT/EP2016/070883 EP2016070883W WO2017037296A1 WO 2017037296 A1 WO2017037296 A1 WO 2017037296A1 EP 2016070883 W EP2016070883 W EP 2016070883W WO 2017037296 A1 WO2017037296 A1 WO 2017037296A1
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formula
ibx
adduct
iii
compound
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PCT/EP2016/070883
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English (en)
Inventor
Simone Mantegazza
Gabriele Razzetti
Emanuele Attolino
Chiara Vladiskovic
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Dipharma Francis S.R.L.
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Publication of WO2017037296A1 publication Critical patent/WO2017037296A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D347/00—Heterocyclic compounds containing rings having halogen atoms as ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms

Definitions

  • the present invention relates to novel adducts of 2-iodoxybenzoic acid, known as IBX, a novel process for the preparation thereof, and their use in alcohol oxidation reactions.
  • DMP Dess- Martin periodinane
  • Both reagents allow a rapid, chemoselective conversion of primary and secondary alcohols to aldehydes and ketones, respectively, and are also used in the oxidation of diols.
  • IBX of formula (I) can be prepared by oxidizing 2-iodobenzoic acid with potassium bromate in aqueous sulfuric acid as described by Greenbaum in Am. J. Pharm. 1936, 108, 17, also used by Dess and Martin in J. Org. Chem. 1983, 48, 4155-4156, or by the safer and more reproducible procedure described by Frigerio and Santagostino in J. Org. Chem. 1999, 64, 4537, which uses potassium peroxymonosulfate (Oxone®) as oxidant in water at 70°C.
  • Oxone® potassium peroxymonosulfate
  • US 2,566,592 claimed formulations containing calcium or ammonium salts of IBX stabilised by the presence of sorbitol
  • US 6,462,227 disclosed a method of preparing a stabilised formulation of IBX (SIBX) obtained by mixing IBX with aliphatic or aromatic carboxylic acids.
  • SIBX stabilised formulation of IBX
  • the formulation benefits from a stabilising effect derived by physical mixing.
  • this is difficult to control at an industrial stage and subject to a possible lack of standardisation of the produced samples at molecular level.
  • PIBX PIBX suspended in an organic solvent, for example in 10 volumes of acetone and stirred overnight, once filtered off resulted to have a pyridine content diminished by about 50%, thus providing a solid with about 50% of free IBX.
  • the invention provides a class of stable adducts with IBX having a defined stoichiometry, which are safer than IBX and PIBX, and a synthesis method for obtaining them, which can be developed on an industrial scale, allowing their synthesis with high reproducibility.
  • adducts of IBX with a compound of formula (III), as defined herein are more soluble than IBX in both organic and aqueous solvent; they are able to oxidize alcohols like IBX, and, no less importantly, have exhibited improved safety characteristics enabling them to be used on an industrial scale.
  • the improved safety properties have been demonstrated by DSC (figures 3-6), wherein the compounds of the present invention exhibited considerably lower decomposition energies than IBX or PIBX.
  • the adducts of IBX with a compound of formula (III) were characterised by nuclear magnetic resonance (NMR) spectrometer, differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD).
  • the X-ray diffraction (XRPD) spectra were collected with a Bruker D8 Advance diffractometer.
  • the detector used was a LynxEye PSD detector.
  • the radiation used was Cu Ka filtered with nickel.
  • the X-ray powder diffraction (XRPD) spectra were collected in the 2 ⁇ range from 3° to 40° with a step size of 0.02°.
  • the DSC patterns were acquired with a Mettler-Toledo DSC 822e differential scanning calorimeter, at the following operating conditions: aluminium capsules, range 30-300°C at the rate of 10°C/min, with nitrogen as purge gas (80 ml/min).
  • Figure 1 XRPD spectrum of the adduct of IBX with nicotinamide wherein the most intense peaks (expressed in ° in 2 ⁇ ) are: 8.25, 1 1.65, 12.59, 13.45, 13.87, 14.34, 16.49, 16.88, 17.48, 20.16, 20.30, 22.15, 23.39, 24.50, 26.10 and 28.84 ⁇ 0.1 °.
  • Figure 2 XRPD spectrum of the adduct of IBX with quinoline, wherein the most intense peaks (expressed in ° in 2 ⁇ ) are: 9.68, 10.78, 1 1.02, 12.1 1 , 14.17, 15.96, 17.1 1 , 17.67, 18.40, 18.78, 19.43, 19.81 , 23.08, 25.28, 26.04 and 27.42 ⁇ 0.1 °.
  • Figure 3 DSC analysis of the adduct of IBX with nicotinamide.
  • Figure 4 DSC analysis of the adduct of IBX with quinoline.
  • Figure 6 DSC analysis of the adduct of IBX with pyridine.
  • Object of the invention is an adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1
  • each of Rl , R2, R3, R4 and R5, which are the same or different, is H, halogen, NO 2 , CN, an optionally substituted Ci-C 6 alkyl or aryl group, an ORa or COORa group wherein Ra is H, or an optionally substituted Ci-C 6 alkyl or aryl group, a CON(RbRc) group, wherein Rb and Rc, which are the same or different, are H, or an optionally substituted Ci-C 6 alkyl or aryl group, or Rb and Rc, taken together with the nitrogen to which they are bound, form a heterocycle; or 1 to 4 of Rl and R2; R2 and R3; R3 and R4; and R4 and R5, taken together, form a C 3 -C 4 alkyl chain, or form an aromatic or a heteroaromatic ring; provided that one of R1 -R5, being as defined above, is not H, and that one or two of R1-R5 are not methyl
  • Ci-C 6 alkyl group which can be straight or branched, is typically a Ci-C 4 alkyl group, optionally substituted by one to three substituents independently selected from halogen, cyano, nitro and phenyl, optionally substituted by one to three substituents independently selected from halogen, and Ci-C 4 alkyl.
  • An aryl group is typically phenyl or naphthyl, preferably phenyl optionally substituted by one to three substituents independently selected from halogen, and Ci-C 4 alkyl.
  • a halogen is preferably fluorine, chlorine bromine or iodine, being in particular fluorine or chlorine.
  • heterocycle when Rb and Rc, taken together with the nitrogen to which they are bound, form a heterocycle, said heterocycle is preferably a saturated heterocycle, such as pyrrolidine, piperidine, piperazine or morpholine, or an unsaturated heterocycle, such as imidazole.
  • the compound of formula (III) thus formed preferably consists of 2 or 3 condensed rings, and is optionally substituted by 1 to 4 substituents selected independently from halogen, NO 2 and CN, an optionally substituted Ci-C 6 alkyl or aryl group, an ORa or COORa group, wherein Ra is H or an optionally substituted Ci-C 6 alkyl or aryl group, and a CON(RdRe) group, wherein Rd and Re, which are the same or different, are H or an optionally substituted Ci-C 6 alkyl or aryl group.
  • the aromatic ring is, for example, phenyl or naphthyl, preferably phenyl.
  • the heteroaromatic ring which can preferably contain 1 to 3 heteroatoms selected independently from oxygen, nitrogen and sulfur is, for example, benzofuran, benzoimidazole, indazole, quinoline, benzothiazole or quinazoline, preferably quinoline.
  • each of Rl , R2, R3, R4 and R5, which are the same or different, is H, an optionally substituted aryl group, a CON(RbRc) group, wherein Rb and Rc, which are the same or different, are H or a C1-C6 alkyl group; or 1 to 2 of Rl and R2; R2 and R3; R3 and R4; and R4 and R5, taken together, form an aromatic or a heteroaromatic ring.
  • Rl is H; R2 is H or CONH2; R3 is H or phenyl; R4 is H or CONH2, and R5 is H; or one of Rl and R2 or R4 and R5, taken together, form a phenyl, naphthalene or quinoline ring, or R2 and R3 or R3 and R4, taken together, form a phenyl ring.
  • Preferred examples of specific compounds of formula (III) are nicotinamide, quinoline, benzo[(g)]quinoline, benzo[h]quinoline, acridine, 9-phenylacridine, phenanthridine and phenanthroline, in particular nicotinamide and quinoline.
  • An adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1 can be prepared, for example, by a process comprising mixing IBX of formula (I) with a compound of formula (III), optionally in a solvent.
  • a compound of formula (III) can be used in a stoichiometric quantity or in excess relative to the amount of IBX of formula (I), preferably over-stoichiometric, for example in a quantity ranging between about 1.0 and 5 equivalents. According to a preferred aspect of the invention, a compound of formula (III) is used in a quantity comprised between about 1.0 and 2.0 equivalents relative to IBX of formula (I).
  • a compound of formula (III) can be added to pure IBX of formula (I) or dissolved in a solvent.
  • a solvent used to form the adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1 can be a polar aprotic solvent, such as dimethylformamide, dimethylsulfoxide or acetonitrile; an ethereal solvent, such as diethyl ether, methyl tert-butyl ether or tetrahydrofuran; a ketone, such as methyl ethyl ketone, methyl isobutyl ketone or acetone; an apolar aprotic solvent, such as hexane, heptane, toluene or xylene; a polar protic solvent, such as a C1-C5 tertiary alkanol, for example tertbutanol, or a Ci-C 4 alkyl carboxylic acid as defined above, or water; or a mixture of two or more, typically two or three, of said solvents.
  • the mixture of IBX of formula (I) and a compound of formula (III) in a solvent, as defined above, can be optionally prepared at a temperature ranging between about - 10°C and the reflux temperature of the solvent, preferably between about 0 and 40°C, more preferably between about 10 and 35°C.
  • the adduct of IBX of formula (I) with a compound of formula (III) can be recovered from the reaction mixture by isolating it as a solid by filtration or centrifugation, as well known to the skilled person. There is no necessity to wash the solid with water.
  • the obtained solid can be washed with a solvent as defined above and stove-dried, optionally under vacuum, to obtain a solid, typically in crystalline form.
  • IBX of formula (I) is a known compound and can be prepared, for example, as described in J. Org. Chem. 1983, 48, 4155-4156.
  • the compound of formula (III) is a known compound with a pyridine core moiety, which is commercially available or can be prepared by well-known methods (Heterocyclic Chemistry / John A. Joule, Keith Mills. - 5th ed. John Wiley & Sons, Ltd., 2010).
  • an adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1 can be prepared by mixing IBX of formula (I) with a compound of formula (III) in a solvent containing water.
  • the decomposition energy of IBX resulted to be 1 163.8 Jg “1 (figure 5), for the adduct of IBX of formula (I) with pyridine (figure 6) 847.5 Jg “1 , while the decomposition energy with 724.3 Jg “1 (figure 3) and 584.1 Jg “1 (figure 4) was considerably lower for the adducts IBX of formula (I) with nicotinamide and quinoline, respectively.
  • a further subject of the present invention is therefore the use of an adduct of IBX of formula (I) with a compound of formula (III) as oxidant in the oxidation reactions of primary and secondary alcohols.
  • Nicotinamide (4.80 g, 39.3 mmol) is added to a suspension of IBX (10.0 g, 35.7 mmol) in methyl isobutyl ketone (50 ml) and water (25 ml) at 25°C, and the mixture is stirred vigorously for 24 hours. The solid is then filtered off, washed with water (10 ml), then with methyl isobutyl ketone (3 x 10 ml), and the product is dried at 30-35°C at low pressure providing 9.8 g of the IBX- nicotinamide adduct (yield 68%).
  • the adduct of IBX with nicotinamide presents an XRPD spectrum, wherein the most intense peaks (expressed in ° in 2 ⁇ ) are 8.25, 1 1.65, 12.59, 13.45, 13.87, 14.34, 16.49, 16.88, 17.48, 20.16, 20.30, 22.15, 23.39, 24.50, 26.10 and 28.84 ⁇ 0.1 °, as illustrated in Figure 1 ; and a DSC pattern as shown in Figure 3.
  • the adduct of IBX with quinoline presents an XRPD spectrum wherein the most intense peaks (expressed in ° in 2 ⁇ ) fall at 9.68, 10.78, 1 1.02, 12.1 1 , 14.17, 15.96, 17.1 1 , 17.67, 18.40, 18.78, 19.43, 19.81 , 23.08, 25.28, 26.04 and 27.42 ⁇ 0.1°, as illustrated in Figure 2; and a DSC pattern as shown in Figure 4.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La présente invention concerne de nouveaux produits d'addition d'acide 2-iodoxybenzoïque, connus sous le nom d'IBX, un nouveau procédé pour leur préparation, et leur utilisation dans des réactions d'oxydation d'alcools.
PCT/EP2016/070883 2015-09-03 2016-09-05 Produits d'addition stables d'acide 2-iodobenzoïque WO2017037296A1 (fr)

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IT102015000048455 2015-09-03
ITUB2015A003373A ITUB20153373A1 (it) 2015-09-03 2015-09-03 Addotti stabili dell?acido 2-iodossibenzoico

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111718323A (zh) * 2020-07-10 2020-09-29 南宁师范大学 高价碘硫氰化试剂及其制备方法与应用

Citations (2)

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US2566592A (en) 1950-07-01 1951-09-04 Smith Kline French Lab Stabilized iodoxy benzoic compounds and the method of producing
US6462227B2 (en) 2001-01-19 2002-10-08 Simafex Stabilized o-iodoxybenzoic acid compositions and process for the preparation thereof

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US2566592A (en) 1950-07-01 1951-09-04 Smith Kline French Lab Stabilized iodoxy benzoic compounds and the method of producing
US6462227B2 (en) 2001-01-19 2002-10-08 Simafex Stabilized o-iodoxybenzoic acid compositions and process for the preparation thereof

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CHEM. ENG. NEWS, 16 July 1990 (1990-07-16)
DESS; MARTIN, J. ORG. CHEM., vol. 48, 1983, pages 4155 - 4156
FRIGERIO; SANTAGOSTINO, J. ORG. CHEM., vol. 64, 1999, pages 4537
GREENBAUM, AM. J. PHARRN., vol. 108, 1936, pages 17
IVAN M KUMANYAEV ET AL: "Pyridinium-iodoxybenzoate as a Safe form of a Famous Oxidant", MENDELEEV COMMUNICATIONS, vol. 22, no. 3, 2012, pages 129 - 131, XP028512072, ISSN: 0959-9436, [retrieved on 20120529], DOI: 10.1016/J.MENCOM.2012.05.004 *
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111718323A (zh) * 2020-07-10 2020-09-29 南宁师范大学 高价碘硫氰化试剂及其制备方法与应用
CN111718323B (zh) * 2020-07-10 2021-06-11 南宁师范大学 高价碘硫氰化试剂及其制备方法与应用

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